Pandossio J E, Brandão M L
Dept. de Psicologia, FFCLRP-USP, Ribeirão Preto, Brasil.
Psychopharmacology (Berl). 1999 Mar;142(4):360-8. doi: 10.1007/s002130050900.
The inferior colliculus is involved in conveying auditory information of an aversive nature to higher cortical structures. Gradual increases in the electrical stimulation of this structure produce progressive aversive responses from vigilance, through freezing, until escape. Recently, we have shown that microinjections of NMDA into the inferior colliculus mimic these aversive effects and that the neural substrates responsible for learned escape behavior in the inferior colliculus are regulated by GABA-benzodiazepine mechanisms. In the present study, we extend these observations showing that unlearned aversive responses are also depressed by muscimol and midazolam, both GABA-benzodiazepine agonists, and that microinjection of glutamate, an excitatory amino acid, into the inferior colliculus can trigger freezing responses. Electrical stimulation of the inferior colliculus of rats placed inside an open field allowed the determination of thresholds for the aversive responses, alertness, freezing and escape. Systemic administration (3 and 5.6 mg/kg) as well as microinjections into the inferior colliculus of the anxiolytic compound midazolam (10, 20 and 40 nmol) caused increases in threshold for these aversive responses. Similar results were obtained following microinjections of the GABA-A agonist muscimol (0.1, 1 and 5 nmol) into this brainstem structure. Microinjections of low doses of glutamate (5 nmol), presumed to activate mainly AMPA/kainate receptors, into the ventrolateral division of the central nucleus of the inferior colliculus of rats placed inside a circular arena induced aversive reactions, characterized by freezing responses. However, higher doses of glutamate caused no apparent effects. GDEE, an AMPA/kainate receptor antagonist, inhibited, whereas AP7, a NMDA receptor antagonist, did not influence these responses. It is suggested that GABA-benzodiazepine processes modulate the expression of defensive reactions in the inferior colliculus and that activation of fast-acting excitatory amino acid receptors in this midbrain region can trigger the initial steps of the defense reaction without eliciting the motor explosive behavior usually seen following the activation of NMDA receptors.
下丘参与将具有厌恶性质的听觉信息传递至更高的皮质结构。对该结构进行电刺激逐渐增强时，会产生从警觉到僵住，直至逃跑的渐进性厌恶反应。最近，我们发现向下丘内微量注射N-甲基-D-天冬氨酸（NMDA）可模拟这些厌恶效应，且下丘中负责习得性逃避行为的神经基质受γ-氨基丁酸-苯二氮䓬机制调控。在本研究中，我们扩展了这些观察结果，表明γ-氨基丁酸-苯二氮䓬激动剂蝇蕈醇和咪达唑仑也会抑制未习得的厌恶反应，并且向下丘内微量注射兴奋性氨基酸谷氨酸能引发僵住反应。对置于旷场内的大鼠的下丘进行电刺激，可确定厌恶反应、警觉、僵住和逃跑的阈值。全身给药（3和5.6毫克/千克）以及向下丘内微量注射抗焦虑化合物咪达唑仑（10、20和40纳摩尔）会导致这些厌恶反应的阈值升高。向下丘这个脑干结构内微量注射γ-氨基丁酸-A激动剂蝇蕈醇（0.1、1和5纳摩尔）后也获得了类似结果。向置于圆形场地内的大鼠下丘中央核腹外侧区微量注射低剂量谷氨酸（5纳摩尔），推测主要激活α-氨基-3-羟基-5-甲基-4-异恶唑丙酸/海人藻酸受体，会引发以僵住反应为特征的厌恶反应。然而，更高剂量的谷氨酸没有产生明显影响。α-氨基-3-羟基-5-甲基-4-异恶唑丙酸/海人藻酸受体拮抗剂GDEE具有抑制作用，而N-甲基-D-天冬氨酸受体拮抗剂AP7则不影响这些反应。研究表明，γ-氨基丁酸-苯二氮䓬过程调节下丘中防御反应的表达，并且该中脑区域快速起效的兴奋性氨基酸受体的激活可触发防御反应的初始步骤，而不会引发通常在N-甲基-D-天冬氨酸受体激活后出现的运动爆发行为。
